Validity and responsiveness of pain rating scales in patients with chronic oral mucosal diseases.

OBJECTIVES: To validate the Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) for measuring pain intensity in chronic oral mucosal diseases. METHODS: Secondary analyses of data including the VAS, NRS, demographic, clinical and quality-of-life outcomes at baseline and 4-month follow-up were retrieved from a clinical study of chronic oral mucosal diseases. Construct and criterion validity and responsiveness of the VAS and NRS were assessed through testing hypotheses based upon strength of Spearman's correlation coefficients. RESULTS: Data of 500 and 290 patients with chronic oral mucosal diseases were used for the assessment of validity and responsiveness, respectively. Moderate-to-high correlations between both pain scores and scores of clinical and quality-of-life outcomes were observed, supporting construct validity of the VAS and NRS. Their criterion validity was confirmed by significantly strong association between scores of both scales. Responsiveness of both scales was adequate based on moderate association between their change scores and global rating of change scale. CONCLUSION: The present results provide evidence supporting validity and responsiveness of the VAS and NRS for pain intensity assessment in patients with chronic oral mucosal diseases. Future research examining other pain intensity domains and standardizing composite scores for pain intensity in this population is required.

A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO).

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. SUBJECTS AND METHODS: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

The patient acceptable symptom state in oral lichen planus: identification of cut-off threshold scores in measures of pain and quality of life.

OBJECTIVES: To establish thresholds of pain and quality of life scores corresponding to patient acceptable symptom state (PASS) in patients with oral lichen planus (OLP) and to assess demographic and clinical factors associated with achieving the PASS. METHODS: Prospective data from baseline and 4-month follow-up including Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), 14-item Oral Health Impact Profile (OHIP-14) and 15-item and 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15; COMDQ-26) were collected from 281 patients with OLP. An anchoring approach based upon the patient's opinion on acceptability of OLP status was applied. Associated factors for achieving the PASS were analysed using multivariate logistic regression. RESULTS: About two-thirds (68.7%) of participants rated their OLP status as acceptable. Cut-off thresholds for PASS were as follows: ≤ 28 mm for VAS, ≤ 3 for NRS, ≤ 18 for total OHIP-14, ≤ 26 for total COMDQ-15 and ≤ 48 for total COMDQ-26. Based upon results of multivariate logistic analysis, factors associated with being in PASS were lower pain intensity, lower depressive symptoms and lower disease activity of OLP. CONCLUSION: The present study established PASS cut-off thresholds as a tool facilitating interpretation of pain and quality of life outcomes relevant to individuals with OLP. CLINICAL RELEVANCE: Identified PASS estimates could be utilised as clinically important endpoints in clinical practice of OLP as well as eligibility criteria for recruiting participants in clinical trials assessing effectiveness of symptomatic intervention of OLP.

Validation of the HADS and PSS-10 and a cross-sectional study of psychological status in patients with recurrent aphthous stomatitis.

OBJECTIVES: To validate the Hospital Anxiety and Depression Scale (HADS) and the 10-item Perceived Stress Scale (PSS-10) for use in clinical studies of recurrent aphthous stomatitis (RAS) and to provide cross-sectional assessment of anxiety, depressive, and distress symptoms and perceived stress in patients with RAS. METHODS: The validity and reliability of the HADS and PSS-10 were evaluated in 120 individuals with RAS through confirmatory factor analysis and calculation of Cronbach's alpha and omega coefficients. The prevalence of comorbid anxiety, depression, distress, and moderate-to-high perceived stress, and their association with demographics and clinical factors were assessed through cutoff scores of the HADS and PSS-10 and bivariate analyses, respectively. RESULTS: A bi-factor model, with all items loading onto general factor with two group factors, provides the best fit to the HADS and PSS-10 data of this RAS cohort. While omega values suggested adequate reliability of total score of both scales, relatively low ranges of coefficient omega hierarchical limit utility of their subscale scores. The prevalence of anxiety, depression, distress, and moderate-to-high perceived stress was 42.5%, 18.33%, 28.33%, and 71.67%, respectively. Ethnicity, alcohol consumption, disease comorbidities, clinical type of RAS, ulcer size, pain, and RAS disease activity were found to be associated with negative psychological symptoms. CONCLUSION: The HADS and PSS-10 are valid and reliable as general scales of psychological distress and stress in patients with RAS. Significant mental burden among RAS patients makes the use of these validated instruments a sensible and prudent practice for psychological assessment of this patient group.

Development and validation of a short version of Chronic Oral Mucosal Disease Questionnaire (COMDQ-15).

BACKGROUND: The adoption of the Chronic Oral Mucosal Disease Questionnaire (COMDQ) into clinical practice has been low, despite its rigorous development process. A potential limitation of the COMDQ is the high response burden to patients. Therefore, the aim of the present study was to develop and validate a short version of the 26-item COMDQ. METHODS: The COMDQ data of 520 patients with chronic oral mucosal diseases were randomly divided into two subsamples. Descriptive item analysis and exploratory factor analysis (EFA) were performed using data from the first subsample for item reduction and development of the shortened COMDQ. The resulting short version was then validated using confirmatory factor analysis (CFA) on the other subsample. Internal consistency reliability of the short-form COMDQ was assessed using Cronbach's alpha. Criterion validity of this new scale was examined against its original version. RESULTS: Based upon item analysis, 11 items were dropped. EFA results on the remaining 15 items extracted four factors consistent with the original COMDQ, and CFA results displayed acceptable goodness-of-fit indices of this factor structure on different sample. The COMDQ-15 was then created. Cronbach's alpha of four subscale scores ranged from 0.7 to 0.91, indicating good internal consistency reliability of the COMDQ-15. Correlations between total and subscale scores of the COMDQ-15 and its parent scale were high, supporting good criterion validity of this shortened scale. CONCLUSION: The COMDQ-15 is a brief, valid and reliable instrument that can give an overview of the patient's quality of life related to their chronic oral mucosal conditions.

Meaningful improvement thresholds in measures of pain and quality of life in oral lichen planus.

OBJECTIVES: To evaluate the responsiveness of measures of pain and oral health-related quality of life (OH-QoL) in patients with oral lichen planus (OLP) and to determine thresholds for minimal important change (MIC) and minimal important difference (MID) for use in this patient population. METHODS: Data from baseline and 4-month follow-up including Visual Analog Scale (VAS), Numerical Rating Scale (NRS), 14-item Oral Health Impact Profile (OHIP-14), 15-item and 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15; COMDQ-26) were collected from 157 patients with OLP. Responsiveness was assessed by testing hypotheses and calculating the area under the curve. MIC and MID were established based on triangulation of distribution-based and anchor-based estimates. RESULTS: The results supported adequate responsiveness of VAS, NRS, COMDQ-15 and COMDQ-26 for use in OLP, while the OHIP-14 demonstrated relatively low sensitivity to detect improvement in the OLP status. Recommended meaningful improvement thresholds were as follows: VAS (MIC 16 mm; MID 18 mm), NRS (MIC/MID 2 points), OHIP-14 (MIC/MID 5 points), COMDQ-15 (MIC 5 points; MID 6 points) and COMDQ-26 (MIC/MID 9 points). CONCLUSION: This study provides some evidence of responsiveness as well as establishing meaningful improvement thresholds in scores of pain and OH-QoL measures in OLP.

Validation of the HADS and PSS-10 and psychological status in patients with oral lichen planus.

OBJECTIVES: To validate the Hospital Anxiety and Depression Scale (HADS) and the 10-item Perceived Stress Scale (PSS-10) for use in patients with oral lichen planus (OLP) and to provide cross-sectional analysis of anxiety, depressive and distress symptoms in patients with OLP. METHODS: Validity and reliability of both instruments were assessed in 260 participants with OLP in one tertiary oral medicine centre through confirmatory factor analysis and calculation of reliability coefficients. Prevalence, clinical and demographic predictors of the presence of psychological symptoms in OLP were calculated and identified using multivariated logistic regression. RESULTS: Factor analysis results demonstrated that a bifactor model described the underlying structure of both scales better than other models. Values of omega indicated adequate reliability of total HADS and PSS-10 score while low coefficient omega hierarchical values limit clinical applicability of their subscale scores. The prevalence of anxiety, depressive and distress symptoms in OLP was 39.23%, 20.77% and 27.69%, respectively. Pain intensity, disease comorbidities, age, smoking and alcohol consumption were found to be independent predictors of the presence of psychological symptoms in OLP. CONCLUSION: The HADS and PSS-10 are appropriate to use as general measures of psychological distress and perceived stress in patients with OLP.

Chronic mucocutaneous candidiasis due to gain-of-function mutation in STAT1.

Chronic mucocutaneous candidiasis (CMC) is a heterogenous group of primary immunodeficiency diseases characterised by susceptibility to chronic or recurrent superficial Candida infection of skin, nails and mucous membranes. Gain-of-function mutations in the STAT1 gene (STAT1-GOF) are the most common genetic aetiology for CMC, and mutation analysis should be considered. These mutations lead to defective responses in Type 1 and Type 17 helper T cells (Th1 and Th17), which, depending on the mutation, also predispose to infection with Staphylococci, Mycobacteria and Herpesviridae. We describe the clinical and genetic findings for three patients with CMC due to gain-of-function mutations in the STAT1 gene.

World Workshop on Oral Medicine VII: Relative frequency of oral mucosal lesions in children, a scoping review.

OBJECTIVE: To detail a scoping review on the global and regional relative frequencies of oral mucosal disorders in the children based on both clinical studies and those reported from biopsy records. MATERIALS AND METHODS: A literature search was completed from 1 January 1990 to 31 December 2018 using PubMed and EMBASE. RESULTS: Twenty clinical studies (sample size: 85,976) and 34 studies from biopsy services (40,522 biopsies) were included. Clinically, the most frequent conditions were aphthous ulcerations (1.82%), trauma-associated lesions (1.33%) and herpes simplex virus (HSV)-associated lesions (1.33%). Overall, the most commonly biopsied lesions were mucoceles (17.12%), fibrous lesions (9.06%) and pyogenic granuloma (4.87%). By WHO geographic region, the pooled relative frequencies of the most common oral lesions were similar between regions in both clinical and biopsy studies. Across regions, geographic tongue (migratory glossitis), HSV lesions, fissured tongue and trauma-associated ulcers were the most commonly reported paediatric oral mucosal lesions in clinical studies, while mucoceles, fibrous lesions and pyogenic granuloma were the most commonly biopsied lesions. CONCLUSIONS: The scoping review suggests data from the clinical studies and biopsy records shared similarities in the most commonly observed mucosal lesions in children across regions. In addition, the majority of lesions were benign in nature.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

BACKGROUND AND OBJECTIVE: Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests. METHODS: We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed. RESULTS: In 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment. CONCLUSIONS: The information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials. CLINICAL TRIAL REGISTRATION: NCT01676077.

Validity and reliability of the Chronic Oral Mucosal Diseases Questionnaire in a UK population.

OBJECTIVE: The objective of this study was to investigate the validity and reliability of a the Chronic Oral Mucosal Diseases Questionnaire in a UK population METHODS: Two hundred patients with chronic oral mucosal disease (oral lichen planus, recurrent aphthous stomatitis, mucous membrane pemphigoid, pemphigus vulgaris) were enrolled in this study from the Oral Medicine Department of University College London Hospitals Trust (UCLHT) Eastman Dental Hospital. Individuals were interviewed using Oral Health Impact Profile (OHIP-14), Visual Analogue Scale (VAS) and Chronic Oral Mucosal Diseases Questionnaire (COMDQ), and the construct validity and internal reliability were examined. RESULTS: Of the 200 study participants, 100 respondents had oral lichen planus, 42 had recurrent aphthous stomatitis and 58 had vesiculobullous conditions (mucous membrane pemphigoid or pemphigus vulgaris). With regard to construct validity, a moderate to good degree of convergent validity was found between OHIP-14 and VAS and most subscales and the total COMDQ score except the patient support subscale of COMDQ (0.21-0.37). CONCLUSION: COMDQ is a valid and reliable patient-reported outcome measure for patients with chronic oral mucosal diseases in a UK population. It can be considered a valuable instrument in both clinical practice and in oral medicine research.

Cost of illness of oral lichen planus in a U.K. population--a pilot study.

OBJECTIVE: To assess the economic burden of oral lichen planus (OLP) from the perspective of the healthcare provider in a U.K. population. METHODS: This prevalence-based cost-of-illness analysis was carried out via a cross-sectional study conducted in the Oral Medicine Unit of the Eastman Dental Hospital. This study was conducted in three phases - phase 1 involved framing of the cost-of-illness analysis, development of the cost inventory and design of the patient questionnaire for ease of data collection. Data collected from patients were inputted during phase 2, and costings were determined. The final phase consisted of the calculation of the cost of illness of OLP. RESULTS: One hundred patients were enrolled in the study, 30 males and 70 females, with an average age of 59.9 years (±13.4 years). The average OLP patient, based on our cohort, attends the oral medicine unit 2.64 times per year, their general medical practitioner 1.13 times annually, their general dental practitioner 0.82 times in a year and fills on average 3.37 prescriptions annually. This leads to an average annual cost of £398.58 (€541.16) per patient per year from the perspective of the healthcare provider. CONCLUSION: The annual average cost of OLP to the healthcare provider in the U.K. is substantial. The prevalence-based cost-of-illness data generated in this study will facilitate comparison with other chronic oral mucosal diseases and with chronic diseases managed in allied medical specialties.

Case report: transpalatal arch resulting in soft tissue damage of the tongue 3 years post-orthodontic treatment.

Whilst transient effects of orthodontic appliances on the oral mucosa are well recognized, chronic lesions, persisting post therapy are unusual. We describe a persistent lingual mucosal defect related to a transpalatal arch (TPA) in a healthy 19-year-old female. The asymptomatic lesion is presently being monitored, however, surgical revision in the future may be requested by the patient if the area fails to remodel. Clinical Relevance: Soft tissue trauma to the tongue by anchorage reinforcing appliances may result in long-term effects that could require surgical management.

Bisphosphonate-related osteonecrosis of the jaws and its relevance to children--a review.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) has been detailed extensively in adults, but to date, there have been no similar cases in children. Members of the dental team may treat children prescribed bisphosphonate therapy often for management of osteogenesis imperfecta (OI). There is uncertainty as to how best treat this patient group. This review explores the background of bisphosphonates, indications for their prescription in children, adverse effects with special emphasis on BRONJ, and protocols available to guide dental management.

Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy.

BACKGROUND: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31 P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. METHODS: Quantitative MRI/31 P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T2 in both global leg and thigh segments and individual muscles and 31 P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31 P MRS markers and functional markers. RESULTS: Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T2 values were found in the anterior part of thigh and leg. Almost all 31 P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pHw , and remained, similar as to water T2 , abnormal for the whole study duration. Global thigh water T2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = -0.55, P = 0.010). CONCLUSIONS: This multi-centre study has shown that quantitative MRI/31 P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb-girdle muscular dystrophy subtypes.

Orofacial granulomatosis: clinical features and long-term outcome of therapy.

BACKGROUND: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by persistent or recurrent soft tissue enlargement, oral ulceration, and a variety of other orofacial features. There remain few detailed reports of the clinical features and long-term response to therapy of substantial groups of patients with OFG. OBJECTIVE: The aim of this study was to determine retrospectively the clinical, hematologic, and histopathological features of a large case series of patients with OFG. In addition the long-term response to therapy was examined. METHODS: Clinically relevant data of 49 patients with OFG who attended a single oral medicine unit in the United Kingdom were retrospectively examined. The analyzed parameters included diagnostic features, clinical manifestations, and outcomes and adverse side effects of therapy. RESULTS: Labial swelling was the most common presenting clinical feature at diagnosis (75.5%), followed by intraoral mucosal features other than ulceration such as cobblestoning and gingival enlargement (73.5%). Mucosal ulceration was observed in 36.7% of patients whereas extraoral facial manifestations such as cutaneous erythema and swelling were present in 40.8% of patients. Of the 45 patients who required treatment, 24 (53.3%) were treated with topical corticosteroids/immunosuppressants only, whereas 21 (46.7%) received a combined therapy (topical plus systemic corticosteroids/immunosuppressants and/or intralesional corticosteroids). The long-term outcome analysis showed complete/partial resolution of tissue swelling and oral ulceration in 78.8% and 70% of patients, respectively. LIMITATIONS: The main limitation of the current study was its retrospective design and methodology including differences in reporting clinical features and outcome. CONCLUSIONS: OFG can show multiple facial and mucosal clinical features. Long-term treatment with topical and/or combined therapy is needed in the majority of patients. Response to therapy is highly variable even though in the long-term complete/partial disease resolution can be obtained in the majority of patients. Mucosal ulceration tends to be more recalcitrant than orofacial swelling. Adverse side effects of therapy are rare.

Thalidomide use in the management of oromucosal disease: A 10-year review of safety and efficacy in 12 patients.

OBJECTIVE: Thalidomide is an effective systemic agent in the management of ulcerative oromucosal conditions. However, its clinical use is limited because of its known adverse effect profile, including teratogenicity, peripheral neuropathy, and thromboembolic risk. The aim of this study was to review the efficacy and safety of thalidomide over a 10-year period in an Oral Medicine specialty clinic. STUDY DESIGN: Clinical records of the Oral Medicine Department at the Royal National ENT and Eastman Dental Hospitals (London, UK) were retrospectively reviewed for patients prescribed thalidomide between 2009 and 2019 for the management of oromucosal ulceration. Twelve eligible patients were identified. Data on patient response to treatment and major/minor adverse events were obtained from their clinical and electrophysiologic records. RESULTS: A complete remission rate was noted in 50% (6 of 12) patients treated for recurrent aphthous stomatitis, HIV-related ulceration and oral Crohn disease. A thalidomide-induced neuropathy rate of 41.7% (5 of 12) was detected by electrophysiology testing, however clinical symptoms of neuropathy were only described by 3 subjects. No other major adverse effects were reported. CONCLUSIONS: Thalidomide demonstrates a good efficacy-to-safety ratio in the management of oromucosal ulceration over a prolonged treatment period. Interval electrophysiologic testing is essential to monitor for thalidomide-induced neuropathy. In this cohort, neuropathy does not appear to be a dose-dependent outcome.

Health-related quality of life and its associated predictors in patients with oral lichen planus: a cross-sectional study.

OBJECTIVES: To investigate levels of quality of life (QoL) and determine associated predictors in patients with oral lichen planus (OLP). MATERIALS AND METHODS: A total of 300 patients with OLP at one tertiary Oral Medicine clinic in the UK were recruited in a cross-sectional study from January 2018 to July 2019. The 15-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15) and 14-item Oral Health Impact Profile (OHIP-14) were used to assess the level of QoL related to OLP. A number of potential determinants were considered, including patient demographics, treatment, the severity of oral symptoms, the clinical activity of the disease, and the patient psychological status, which were measured using the pain-Numerical Rating Scale, the Oral Disease Severity Score, the Hospital Anxiety and Depression Scale, and the 10-item Perceived Stress Scale. Multivariate linear regression was employed to identify independent determinants associated with overall and aspects of QoL. RESULTS: On multivariate analyses, after adjusting for confounding variables, the QoL levels in patients with OLP were significantly associated with levels of oral pain, anxiety, stress and use of topical corticosteroids. The COMDQ-15 instrument performed better than OHIP-14 at capturing the association between QoL and pain and disease activity in patients with OLP. CONCLUSION: Clinicians should expect reduced QoL in OLP patients with high pain levels, high anxiety levels, high perceived stress and use of topical corticosteroids. The COMDQ-15 is best suited to measure QoL in this population.